We report for the first time that negatively charged silica nanoparticles (NPs) enhance the ability of cationic surfactants to induce genomic DNA compaction. Single-chain compaction of duplex DNA molecules was studied by fluorescence microscopy in the presence of dodecyltrimethylammonium bromide (DTAB) and NPs. We found that very small amounts of NPs (∼10−4 to 10−2 wt%) significantly decreased the concentration of the surfactant at which DNA is compacted. This effect was maximal at intermediate NP concentration (here, 1.5 × 10−3 wt%) where the concentration of DTAB necessary for DNA compaction was 5-fold smaller than that in the absence of NPs. As a possible mechanism, we suggest that negatively charged NPs, by inducing the aggregation of DTAB molecules through electrostatic interactions, promote cooperative binding to DNA and thus enhance the ability of DTAB to compact DNA. By applying this phenomenon to a photosensitive cationic surfactant (AzoTAB), we could achieve reversible control of DNA higher-order structure using light at a much lower AzoTAB concentration than what has been reported up to now.